Chemo-photodynamic Activity of Silicon Phthalocyanines Bearing Cyclooxygenase Inhibitors on Colorectal Cancer Cell Lines.

Colorectal cancer ranks as the third most lethal cancer worldwide, resulting in over 1 million cases and 900 000 deaths per year. According to population-based studies, administration of long-term non-steroidal anti-inflammatory drugs (NSAIDs) was proven to reduce the risk of a subject developing colorectal cancer. In the present study, the anti-cancer activity of two different NSAIDs, sulindac- (Pc-1) or diclofenac-substituted (Pc-2) asymmetric silicon phthalocyanine derivatives, was evaluated in four different colorectal cancer cell lines bearing various carcinogenic mutations. In this context, the IC50 values of each compound after 24 and 48 h were determined on HCT116, SW480, LoVo, and HT29 cell lines, and the effects of the compounds on programmed cell death pathways apoptosis and autophagy, their impact on cell cycle progression, and the effect of NSAID moieties they bear on COX-1 and COX-2 proteins were analyzed. In addition, the photophysical and photochemical properties of a synthesized Pc derivative bearing axial diclofenac and triethylene glycol groups (Pc-2) have been investigated, and the compound has been characterized by using different analytical techniques. Our results indicated that both compounds inhibit COX protein expression levels, activate apoptosis in all cell lines, and lead to cell cycle arrest in the G2/M phase, depending on the COX expression profiles of the cell lines, indicating that NSAIDs can be coupled with Pc's to achieve increased anti-cancer activity, especially on cancer cells known to have high COX activity.

Novel axially symmetric and unsymmetric silicon(IV) phthalocyanines having anti-inflammatory groups: synthesis, characterization and their biological properties.

New asymmetric Si(IV)Pc (1), monomeloxicammonotriethyleneglycolmonomethylether (phthalocyaninano)silicone, axially ligated with meloxicam as a non-steroidal anti-inflammatory drug (NSAID), or triethylene glycol monomethyl ether and symmetric Si(IV)Pc (2), diclofenac(phthalocyaninano)silicone, axially ligated with two diclofenac as NSAID, were synthesized and characterized as antioxidant and antimicrobial agents together with polyoxo-SiPc (3), ditriethyleneglycolmonomethylether(phthalocyaninano)silicone, and SiPc(OH)2 (4), dihydroxy(phthalocyaninano)silicone. The photophysical and photochemical properties of these compounds were investigated. Then, antioxidant assays, including 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferrous ion chelating activities, were performed for these Si(IV) phthalocyanine derivatives (1, 2, 3 and 4). The highest DPPH scavenging activity of 73.48% was achieved with compound 2 and the highest ferrous chelating ability of 66.42% was obtained with compound 3. The results of the antioxidant assays indicated that Pc derivatives 1, 2 and 3 have remarkable superoxide radical scavenging activities, and moderate 2,2-diphenyl-1-picrylhydrazyl activities and metal chelating activities. The antimicrobial effects of the Si(IV) phthalocyanine compounds were studied against six pathogenic bacteria and two pathogenic microfungi. The results for the antimicrobial activity of these compounds indicated that Enterococcus faecalis (ATCC 29212) was the most sensitive microorganism and Pseudomonas aeruginosa (ATCC 27853) and Legionella pneumophila subsp. pneumophila (ATCC 33152) were the most resistant microorganisms against the tested compounds. The DNA cleavage ability and microbial cell viability of these compounds were studied. The studied compounds demonstrated excellent DNA nuclease activity and exhibited 100% cell viability inhibition at 500 mg L-1. Also, the antimicrobial photodynamic therapy of the compounds was tested against Escherichia coli (ATCC 25922) and significant photodynamic antimicrobial activity was observed. In addition, the effect of phthalocyanines on biofilm inhibition produced by Staphylococcus aureus (ATCC 25923) was also tested and 3 showed excellent biofilm inhibition of 82.14%.

Synthesis, Photophysical and Photochemical Properties of a Set of Silicon Phthalocyanines Bearing Anti-Inflammatory Groups.

In this study, a series of novel silicon (IV) phthalocyanines conjugated axially with anti-inflammatory (sulindac) and triethylene glycol groups has been synthesized. Different synthetic strategies were attempted to obtain the targeted molecules in high yield. The compounds were fully characterized by using different analyses techniques. Our objectives were to generate a system with sulindac group which enhances the singlet oxygen generation and exhibits anti-cancer effect. Therefore, photophysical and photochemical properties of these compounds were investigated in different solvents. The substituent effect on fluorescence quantum yield and singlet oxygen generation was evaluated for efficiency in photodynamic therapy (PDT) as photosensitizer. The molecules exhibited no aggregation tendency, solubility in common organic solvents, high singlet oxygen quantum yield and high photostability in DMSO so these favourable properties make them good candidates as photosensitizer for PDT. In addition, their stabilities were investigated in DMSO, THF, acetonitrile and DMF.